NALOREX 50 mg film-coated tablets
(Naltrexone hydrochloride)
PHARMACOTHERAPEUTIC CATEGORY
Drugs used in addiction.
THERAPEUTIC INDICATIONS
NALOREX is indicated as adjunctive preventive therapy to maintain opioid detoxification in former opioid-dependent patients.
NALOREX is also indicated as part of a comprehensive treatment program for alcohol dependence to reduce the risk of relapse, promote abstinence, and reduce the urge to consume alcoholic beverages during the initial phases of treatment.
CONTRAINDICATIONS
NALOREX is contraindicated:

in patients with acute hepatitis, hepatic failure, or decompensated liver cirrhosis.
in opioid-dependent patients, as it may precipitate an acute withdrawal syndrome.
in patients who test positive for opioids or who have tested positive in a naloxone challenge test.
in patients with known hypersensitivity to naltrexone hydrochloride or any of the excipients.
in patients with severe renal impairment.
in combination with methadone (see the section "Interactions").
when used concomitantly with opioid-containing medicines.
in pediatric patients. NALOREX is generally contraindicated during pregnancy and lactation.

PRECAUTIONS FOR USE
Treatment must be initiated and continued under the supervision of a specialist in the treatment of opioid or alcohol dependence, in accordance with national guidelines.
Since NALOREX is primarily metabolized in the liver and mainly excreted via urine, particular caution is required when administering it to patients with impaired hepatic or renal function.
Liver function tests should be performed both before and during treatment.
Abnormalities in liver function tests have been reported after naltrexone administration in obese patients and elderly patients without a history of drug abuse. Liver function tests must be performed both before and during treatment.
Opioid-dependent individuals may frequently present with impaired liver function, which may also be observed in alcohol-dependent subjects. Alterations in liver function tests have been reported in elderly obese patients taking naltrexone at doses higher than recommended (up to 300 mg/day) for the treatment of alcoholism. Liver function tests should be performed before and periodically during therapy.
NALOREX may precipitate an acute withdrawal syndrome in opioid-dependent patients; signs and symptoms of withdrawal may appear within 5 minutes and last up to 48 hours. In such cases, symptomatic treatment should be initiated, which may include administration of an opioid.
A naloxone challenge test is recommended to verify possible opioid use: withdrawal syndrome induced by naloxone hydrochloride is shorter in duration compared to that caused by NALOREX.
The naloxone challenge test must not be performed in patients with evident signs of withdrawal or in patients whose urine tests positive for opioids.
Treatment with naltrexone should only begin after opioid use has been discontinued for a sufficiently long period (approximately 5–7 days for heroin and at least 10 days for methadone).
Patients must be informed that attempts to overcome the blockade caused by the drug by using high doses of opioids may result in acute opioid intoxication, potentially life-threatening, once the effect of naltrexone wears off. The use of high opioid doses in combination with naltrexone treatment may cause acute opioid poisoning leading to respiratory and circulatory failure, which may be life-threatening.
Patients must therefore be warned of the risks associated with concomitant use of opioids (e.g. cough preparations, cold remedies, or anti-diarrheal medications, etc.) during naltrexone treatment.
In emergency situations requiring administration of an opioid analgesic to a patient taking NALOREX, a higher than normal dose of opioid may be required to achieve the same therapeutic effect. Respiratory depression may be deeper and more prolonged, and non-receptor-mediated effects may also occur (e.g. facial edema, pruritus, generalized erythema, diaphoresis, and other skin and mucous membrane symptoms, presumably due to histamine release). In such circumstances, the patient must be closely monitored by qualified personnel in a hospital setting.
It is known that the risk of suicide is increased in drug-dependent patients, regardless of concomitant depressive disorders. This risk is not reduced by treatment with NALOREX (see section “Adverse Effects”).
INTERACTIONS
Patients taking naltrexone may become unresponsive to the effects of opioid-containing medicines, such as cough and cold remedies, anti-diarrheal preparations, and opioid analgesics.
Patients must be warned of the danger, sometimes fatal, of increasing opioid doses in an attempt to overcome the blockade caused by the drug.
In emergency situations requiring opioid analgesia, a higher dose may be needed to effectively control pain. The patient must be closely monitored for possible respiratory depression or other adverse effects. Clinical experience and experimental data on the effect of naltrexone on the pharmacokinetics of other substances are limited. Concomitant treatment with naltrexone and other medicines should therefore be conducted with caution and closely monitored. No interaction studies have been performed.
In vitro studies have shown that neither naltrexone nor its main metabolite, 6-β-naltrexol, are metabolized by human CYP450 enzymes. Therefore, it is unlikely that the pharmacokinetics of naltrexone will be affected by cytochrome P450 inhibitors.
Not recommended combinations: opioid substances (analgesics, antitussives, opioids used in substitution therapy), centrally-acting antihypertensives (alpha-methyldopa).
Concomitant administration of naltrexone with an opioid-containing medicine must be avoided.
Concomitant use of methadone for substitution therapy is not recommended: there is a risk of withdrawal syndrome.
Combinations requiring precautions in use:
Barbiturates, benzodiazepines, non-benzodiazepine anxiolytics (e.g. meprobamate), hypnotics, sedative antidepressants (amitriptyline, doxepin, mianserine, trimipramine), sedative H1 antihistamines, neuroleptics (droperidol).
Currently, there is no evidence of an interaction between naltrexone and cocaine.
A safety and tolerability study on the co-administration of naltrexone and acamprosate in alcohol-dependent subjects not seeking treatment showed that naltrexone significantly increases plasma levels of acamprosate. No interaction studies have been conducted with other substances acting on the central nervous system (disulfiram, amitriptyline, doxepin, lithium, clozapine, benzodiazepines).
No interactions between naltrexone and alcohol are known.
Cases of lethargy and somnolence have been reported following concomitant administration of naltrexone and thioridazine.
SPECIAL WARNINGS
Pregnancy and lactation
Pregnancy
There are no clinical data on the use of naltrexone hydrochloride during pregnancy. Animal studies have shown reproductive toxicity. Data are insufficient to determine clinical relevance. The potential risk in humans is unknown. Naltrexone should be used during pregnancy only when, in the opinion of the treating physician, the potential benefits outweigh the possible risks.
The use of naltrexone in pregnant patients undergoing long-term treatment with opioids or opioid substitution therapy, or in opioid-dependent patients, carries a risk of acute withdrawal syndrome, which may have serious consequences for both mother and fetus (see section “Precautions for Use”).
Administration of naltrexone should be suspended if opioid analgesics are prescribed (see section “Interactions”).
Lactation
There are no clinical data on the use of naltrexone hydrochloride during lactation. It is unknown whether naltrexone or 6-beta-naltrexol are excreted in breast milk. Breastfeeding is therefore not recommended during naltrexone therapy.
Effects on ability to drive and use machines
NALOREX may impair mental and/or physical abilities required for potentially hazardous activities such as driving a car or operating machinery.
Important information about certain excipients
Lactose: patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take NALOREX.
DOSAGE, ADMINISTRATION AND TREATMENT DURATION
NALOREX administration must not be initiated unless a naloxone challenge test has been performed and yielded a negative result.
Naloxone Challenge Test
Intravenous challenge test: administer 0.2 mg of naloxone intravenously. If no adverse reactions occur after 30 seconds, an additional intravenous dose of 0.6 mg of naloxone may be administered. Continue to observe the patient for at least 20 minutes to monitor for signs of withdrawal.
Subcutaneous challenge test: administer 0.8 mg of naloxone subcutaneously. Observe the patient for at least 20 minutes to monitor for signs and symptoms of withdrawal.
Confirmation of challenge test: if there is any doubt about opioid use, treatment with NALOREX should be delayed for 24 hours, and the challenge test repeated with 1.6 mg of naloxone.
Treatment with NALOREX should only be considered for patients who have been opioid-free for at least 7–10 days.
Before initiating treatment with NALOREX, a negative naloxone test must be confirmed by urine analysis. Therapy should begin with low doses of naltrexone, as specified in the treatment program.
The recommended dose of naltrexone is 50 mg daily (1 tablet). Administration three times a week (e.g. 100 mg on Monday, 100 mg on Wednesday, and 150 mg on Friday) may be considered if this improves patient adherence to the treatment regimen.
A daily dose exceeding 150 mg is not recommended, as it may increase the incidence of adverse effects.
Since NALOREX is an adjunctive therapy and complete remission from opioid or alcohol dependence varies among individuals, no standard treatment duration can be recommended. An initial treatment period of three months should be considered. However, longer treatment periods may be necessary.
Use in children: NALOREX is not recommended for patients under 18 years of age. Safety and efficacy have not been established in children.
Use in elderly patients: Safety and efficacy have not been established in elderly patients for the treatment of alcoholism or opioid dependence.
OVERDOSE
Clinical experience with NALOREX overdose is limited. Although no signs of toxicity were observed in healthy volunteers who took 800 mg/day for 7 days, in case of overdose, patients should be monitored and treated symptomatically in a specialized setting.
ADVERSE EFFECTS
Like all medicines, NALOREX can cause adverse effects, although not everyone experiences them.
Adverse effects observed with naltrexone are similar in both alcoholic and opioid-dependent populations. Serious adverse reactions are not common.
The following adverse reactions have been more frequently reported during naltrexone therapy: nervousness, anxiety, insomnia, headache, restlessness, abdominal pain, nausea and/or vomiting, arthralgia and myalgia, asthenia.
Depression, suicidal ideation, and suicide attempts have been reported in patients taking NALOREX, placebo, and in control groups undergoing detoxification treatment. Although no causal relationship with NALOREX has been suspected, physicians should be aware that treatment with NALOREX does not reduce the risk of suicide in these patients (see section “Precautions for Use”).
The following adverse effects have been reported at the beginning and during naltrexone use. Frequency is defined according to the following convention: very common (>1/10); common (>1/100, <1/10); uncommon (>1/1,000, <1/100); rare (>1/10,000, <1/1,000); very rare (<1/10,000).
Blood and lymphatic system disorders
Uncommon: lymphadenopathy
Rare: idiopathic thrombocytopenic purpura
Psychiatric disorders
Very common: nervousness, anxiety, insomnia
Common: irritability, affective disorders
Uncommon: hallucinations, confusion, depression, paranoia, disorientation, nightmares, agitation, libido disorders, abnormal dreams
Rare: suicidal ideation, suicide attempt
Nervous system disorders
Very common: headache, restlessness
Common: dizziness
Uncommon: tremor, somnolence
Eye disorders
Common: increased lacrimation
Uncommon: blurred vision, eye irritation, photophobia, ocular edema, eye pain, asthenopia
Cardiac disorders
Common: tachycardia, palpitations, ECG changes
Vascular disorders
Uncommon: blood pressure fluctuations, hot flushes
Respiratory, thoracic and mediastinal disorders
Common: chest pain
Uncommon: nasal congestion, nasal discomfort, rhinorrhea, sneezing, oropharyngeal pain, increased sputum, sinusitis, dyspnea, dysphonia, cough, yawning
Gastrointestinal disorders
Very common: abdominal pain, nausea and/or vomiting
Common: diarrhea, constipation
Uncommon: flatulence, hemorrhoids, ulcer, dry mouth
Hepatobiliary disorders
Uncommon: liver disorders, increased blood bilirubin, hepatitis (during therapy, elevated liver transaminases may occur. After discontinuation of NALOREX, transaminase levels return to baseline within several weeks)
Skin and subcutaneous tissue disorders
Common: skin rash
Uncommon: seborrhea, pruritus, acne, alopecia
Musculoskeletal and connective tissue disorders
Very common: arthralgia and myalgia
Uncommon: groin pain
Very rare: rhabdomyolysis
Reproductive system and breast disorders
Common: delayed ejaculation, erectile dysfunction
Renal and urinary disorders
Uncommon: pollakiuria, dysuria
Ear and labyrinth disorders
Uncommon: ear disorders, ear pain, tinnitus, vertigo
Infections and infestations
Uncommon: oral herpes, tinea pedis
Metabolism and nutrition disorders
Common: decreased appetite
General disorders
Very common: asthenia
Common: thirst, increased energy, chills, hyperhidrosis
Uncommon: increased appetite, weight loss, weight gain, pyrexia, pain, cold sensation in extremities, hot sensation
Following the instructions in this leaflet reduces the risk of adverse effects.
If any of the adverse effects worsens, or if any adverse effect not listed in this leaflet occurs, inform your doctor or pharmacist.
EXPIRY DATE AND STORAGE
Expiry date: see the date on the packaging
The expiry date refers to the product in its original, unopened packaging, correctly stored.
WARNING: do not use the medicine after the expiry date stated on the packaging.
MEDICINES MUST NOT BE DISPOSED OF VIA WASTEWATER OR HOUSEHOLD WASTE.
Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
Keep the medicine out of the reach and sight of children.
COMPOSITION
One film-coated tablet contains:
Active substance:
Naltrexone hydrochloride 50 mg
Excipients:
Lactose monohydrate, microcrystalline cellulose, crospovidone, colloidal silicon dioxide, magnesium stearate. Coating constituents: Opadry yellow.
PHARMACEUTICAL FORM AND CONTENT
Film-coated tablets, box of 14 tablets
MARKETING AUTHORIZATION HOLDER
L. Molteni & C. dei F.lli Alitti Società di Esercizio S.p.A
Strada Statale 67 Fraz. Granatieri – SCANDICCI (FI)
MANUFACTURER
Istituto De Angeli srl – loc. PRULLI – Reggello (FI)
L. Molteni & C. dei F.lli Alitti Società di Esercizio SpA – S.S. 67 – Granatieri – Scandicci (FI)

Nalorex